miRNAs Plasma Profiles in Vascular Dementia: Biomolecular Data and Biomedical Implications

Abstract

Vascular dementia (VaD) is a pathogenetically heterogeneous neuropsychiatric syndrome, mainly characterized by cognitive impairment. Among dementias, it is second by incidence after Alzheimer’s dementia (AD). VaD biomolecular bases have been poorly characterized, but vascular-linked factors affecting the CNS and its functions are generally hypothesized to perform a major role, together with cardiovascular and immunological factors. miRNAs, which perform critically important biomolecular roles within cell networks, are also found in biological fluids as circulating miRNAs (cmiRNAs). We hypothesized that differentially expressed (DE) cmiRNAs in plasma from VaD patients could be applied to diagnose VaD through liquid biopsies; these profiles also could allow to start investigating VaD molecular bases. By exploiting TaqMan Low-Density Arrays and single TaqMan assays, miR-10b*, miR29a-3p, and miR-130b-3p were discovered and validated as significantly downregulated DE cmiRNAs in VaD patients compared to unaffected controls (NCs). These miRNAs also were found to be significantly downregulated in a matched cohort of AD patients, but miR-130b-3p levels were lower in AD than in VaD. A negative correlation was detected between miR-29a and miR-130b expression and cognitive impairment in VaD and AD, respectively. Receiver operating characteristic curves demonstrated that decreased plasma levels of miR-10b*, miR29a-3p, and miR-130b-3p allow to discriminate VaD and AD patients from NCs. Furthermore, the concurrent downregulation of both miR-10b* and miR-130b-3p in VaD showed an area under the curve (AUC) of 0.789 (p < 0.0001) with 75% of sensitivity and 72% of specificity, whereas an AUC of 0.789 (p < 0.0001) with 92% of sensitivity and 81% of specificity was found for both in AD. The miRNAs profiles reported in this paper pave the way to translational applications to molecular VaD diagnosis, but they also should allow to further investigate on its molecular bases.

Expression and Regulatory Network Analysis of miR-140-3p, a New Potential Serum Biomarker for Autism Spectrum Disorder

“…Stability, general consistency of expression among individuals, and condition-specific expression profile make circulating miRNAs appropriate non-invasive diagnostic biomarkers (Weiland et al, 2012 ; Larrea et al, 2016 ). Expression profiling of miRNAs circulating in either serum or plasma has already been used as a biomarker discovery approach for several psychiatric disorders (Rong et al, 2011 ; Balakathiresan et al, 2014 ; Rizzo et al, 2015 ; Wang et al, 2015a , b ; Wang X. et al, 2015 ; Wei et al, 2015 ; Wu et al, 2015 ; An et al, 2016 ; Ragusa et al, 2016 ; Di Pietro et al, 2017 ).…”

“…Preamplified products were loaded on TaqMan Human MicroRNA Array v3.0 A and B 384-well microfluidic cards (Applied Biosystems, Foster City, CA, USA). PCR reactions on TLDAs were performed on a 7900HT Fast Real Time PCR System (Applied Biosystems) (Ragusa et al, 2016 ).…”

“…Stability and general consistency of levels among individuals, along with the existence of specific expression signatures in association with both physiological and pathological conditions, make circulating miRNAs appropriate biomarkers; these also suggest the prospective alternative use of liquid biopsies as sources of biomarkers in the clinic (Weiland et al, 2012 ; Larrea et al, 2016 ). Numerous studies have identified either serum or plasma circulating miRNAs as promising biomarkers for neurodevelopmental and neuropsychiatric disorders, as ADHD (Wu et al, 2015 ), TS (Rizzo et al, 2015 ), depression/anxiety disorder (Wang X. et al, 2015 ), posttraumatic stress disorder (Balakathiresan et al, 2014 ), bipolar disorder (Rong et al, 2011 ), schizophrenia (Wei et al, 2015 ), and epilepsy (Wang et al, 2015a , b ; An et al, 2016 ), and other brain pathological conditions, like traumatic brain injury (Di Pietro et al, 2017 ) and vascular dementia (Ragusa et al, 2016 ).…”

“…Following profiling of serum miRNAs through our previously published protocol (Rizzo et al, 2015 ; Ragusa et al, 2016 ), we validated serum miR-140-3p as significantly upregulated in ASD patients compared to unaffected controls (NCs), TS patients, and TS+ASD patients. Also, we demonstrated that its serum expression levels are correlated with scores from the tic scale YGTSS (Yale Global Tic Severity Scale).…”

Salivary Redox Biomarkers in Selected Neurodegenerative Diseases

“…According to the World Health Organization (WHO), in 2015, the condition affected 47 million people worldwide, which is approximately 5% of the elderly population [56]. Alzheimer's disease-related dementias are classified as Alzheimer's dementia (AD), frontotemporal dementia (FTD), dementia with Lewy bodies (DLB), vascular dementia (VaD), as well as mixed dementias (MxD) [57]. The main signs of AD pathogenesis are the existence of tau neurofibrillary tangles (NFTs) and amyloid-β (Aβ) plaques, which lead to synaptic loss [58].…”